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Objective: To address the comparative effectiveness of common interventional procedures for chronic non-cancer (axial or radicular) spine pain., Design: Systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs)., Data Sources: Medline, Embase, CINAHL, CENTRAL, and Web of Science from inception to 24 January 2023., Study Selection: RCTs that enrolled patients with chronic non-cancer spine pain, randomised to receive a commonly used interventional procedure versus sham procedure, usual care, or another interventional procedure., Data Extraction and Synthesis: Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence., Results: Of 132 eligible studies, 81 trials with 7977 patients that explored 13 interventional procedures or combinations of procedures were included in meta-analyses. All subsequent effects refer to comparisons with sham procedures. For chronic axial spine pain, the following probably provide little to no difference in pain relief (moderate certainty evidence): epidural injection of local anaesthetic (weighted mean difference (WMD) 0.28 cm on a 10 cm visual analogue scale (95% CI -1.18 to 1.75)), epidural injection of local anaesthetic and steroids (WMD 0.20 (-1.11 to 1.51)), and joint-targeted steroid injection (WMD 0.83 (-0.26 to 1.93)). Intramuscular injection of local anaesthetic (WMD -0.53 (-1.97 to 0.92)), epidural steroid injection (WMD 0.39 (-0.94 to 1.71)), joint-targeted injection of local anaesthetic (WMD 0.63 (-0.57 to 1.83)), and joint-targeted injection of local anaesthetic with steroids (WMD 0.22 (-0.42 to 0.87)) may provide little to no difference in pain relief (low certainty evidence); intramuscular injection of local anaesthetic with steroids may increase pain (WMD 1.82 (-0.29 to 3.93)) (low certainty evidence). Evidence for joint radiofrequency ablation proved of very low certainty.For chronic radicular spine pain, epidural injection of local anaesthetic and steroids (WMD -0.49 (-1.54 to 0.55)) and radiofrequency of dorsal root ganglion (WMD 0.15 (-0.98 to 1.28)) probably provide little to no difference in pain relief (moderate certainty evidence). Epidural injection of local anaesthetic (WMD -0.26 (-1.37 to 0.84)) and epidural injection of steroids (WMD -0.56 (-1.30 to 0.17)) may result in little to no difference in pain relief (low certainty evidence)., Conclusion: Our NMA of randomised trials provides low to moderate certainty evidence that, compared with sham procedures, commonly performed interventional procedures for axial or radicular chronic non-cancer spine pain may provide little to no pain relief., Registration: PROSPERO (CRD42020170667)., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare: no financial support from any industry for the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice., Objective: To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID., Methods: Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice., Conclusion: This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations., Ethics and Dissemination: The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online., Competing Interests: Competing interests: RSM has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie and Atai Life Sciences. RSM is a CEO of Braxia Scientific., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the effectiveness of interventions for the management of long covid (post-covid condition)., Design: Living systematic review., Data Sources: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023., Eligibility Criteria: Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care., Results: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference -5.2, -7.97 to -2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference -1.50, -2.41 to -0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range -0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid., Conclusion: Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid., Systematic Review Registration: Open Science Framework https://osf.io/9h7zm/., Readers' Note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Long COVID Web and the Canadian Institutes of Health Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To address the efficacy and safety of proactive therapeutic drug monitoring of biologic drugs for patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis., Design: Systematic review and meta-analysis., Data Sources: Medline, Embase, Central, and CINAHL, from database inception to 23 May 2024., Eligibility Criteria for Selecting Studies: Trials including people with inflammatory bowel disease, inflammatory arthritis, and psoriasis were selected. Selected trials also randomly assigned people to either proactive therapeutic drug monitoring of tumour necrosis factor-alpha inhibitors or other biologic drugs in the intervention group, and to either no therapeutic drug monitoring or standard care in the control group. Reviewers worked independently and in duplicate to screen search records and collect data from eligible trials. For each outcome, a frequentist, pairwise, random effects meta-analysis was done and the certainty of evidence was assessed using GRADE (grading of recommendations, assessment, development, and evaluations)., Results: Of 10 eligible trials identified, reporting on 2383 patients, two investigated induction with infliximab (533 patients), four assessed maintenance with infliximab (901 patients), and three assessed maintenance with adalimumab (710 patients). One trial was of maintenance with infliximab, adalimumab, and etanercept (239 patients). For patients who had induction with infliximab, the effects of proactive therapeutic drug monitoring on remission and adverse events were uncertain. Low certainty evidence suggested that proactive therapeutic drug monitoring may have little or no effect on disease activity, physical function, mental health, and quality of life. For patients who had maintenance with infliximab, low certainty evidence suggested that proactive therapeutic drug monitoring may increase the proportion of patients who had sustained disease control or remission (relative risk 1.26 (95% confidence interval (CI) 1.14 to 1.40), absolute risk difference of 146 more per 1000 patients treated for one year (95% CI 78 to 224). Additionally, this treatment and monitoring may reduce disease worsening, and may have little or no effect on disease activity, physical function, mental health, and quality of life. The effects of proactive therapeutic drug monitoring of infliximab on adverse events and formation of anti-drug antibodies were uncertain. For patients who had maintenance with adalimumab, the effects of proactive therapeutic drug monitoring were uncertain., Conclusion: Proactive therapeutic drug monitoring of infliximab during maintenance may help patients to have sustained disease control or remission. No compelling evidence supported the effectiveness of proactive therapeutic drug monitoring of infliximab during induction or proactive therapeutic drug monitoring of adalimumab during maintenance., Systematic Review Registration: https://osf.io/x4m28/., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the European Union’s Horizon Europe research and innovation programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; DZ is a member of the editorial board of BMJ Medicine, but had no involvement in the editorial decisions or peer review process regarding this manuscript; all editorial procedures, including the handling of this submission, were conducted independently; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA)., Methods: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence., Results: We included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty)., Conclusions: Intra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In recent studies, receipt of chiropractic care has been associated with lower odds of receiving prescription opioids and, among those already prescribed, reduced doses of opioids among patients with non-cancer spine pain. These findings suggest that access to chiropractic services may reduce reliance on opioids for musculoskeletal pain., Objective: To assess the impact of chiropractic care on initiation, or continued use, of prescription opioids among patients with non-cancer spine pain., Methods: We will search for eligible randomized controlled trials (RCTs) and observational studies indexed in MEDLINE, Embase, AMED, CINAHL, Web of Science, and the Index to Chiropractic Literature from database inception to June 2024. Article screening, data extraction, and risk-of-bias assessment will be conducted independently by pairs of reviewers. We will conduct separate analyses for RCTs and observational studies and pool binary outcomes (e.g. prescribed opioid receipt, long-term opioid use, and higher versus lower opioid dose) as odds ratios (ORs) with associated 95% confidence intervals (CIs). When studies provide hazard ratios (HRs) or relative risks (RRs) for time-to-event data (e.g. time-to-first opioid prescription) or incidence rates (number of opioid prescriptions over time), we will first convert them to an OR before pooling. Continuous outcomes such as pain intensity, sleep quality, or morphine equivalent dose will be pooled as weighted mean differences with associated 95% CIs. We will conduct meta-analyses using random-effects models and explore sources of heterogeneity using subgroup analyses and meta-regression. We will evaluate the certainty of evidence of all outcomes using the GRADE approach and the credibility of all subgroup effects with ICEMAN criteria. Our systematic review will follow the PRISMA statement and MOOSE guidelines., Discussion: Our review will establish the current evidence informing the impact of chiropractic care on new or continued prescription opioid use for non-cancer spine pain. We will disseminate our results through peer-reviewed publication and conference presentations. The findings of our review will be of interest to patients, health care providers, and policy-makers., Trial Registration: Systematic review registration: PROSPERO CRD42023432277., (© 2024. The Author(s).)

Background: Surgical site infections continue to be a significant challenge following colorectal surgery. These can result in extended hospital stays, hospital readmissions, increased treatment costs, and negative effects on patients' quality of life. Antibiotic prophylaxis plays a crucial role in preventing infection during surgery, specifically in preventing surgical site infections after colorectal surgery in adult patients. However, the optimal antibiotic regimen is still unclear based on current evidence. Considering the limitations of existing reviews, our goal is to conduct a comprehensive systematic review and network meta-analysis of randomized controlled trials to evaluate the comparative benefits and harms of available antibiotic prophylaxis regimens for preventing surgical site infections following colorectal surgery in adult patients., Methods: We will search the Medline, EMBASE, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases to identify relevant randomized controlled trials. We will include trials that (1) enrolled adults who underwent colorectal surgeries and (2) randomized them to any systemic administration of antibiotic (single or combined) prophylaxis before surgery compared to an alternative systemic antibiotic (single or combined antibiotic), placebo, control, or no prophylactic treatment. Pairs of reviewers will independently assess the risk of bias among eligible trials using a modified Cochrane risk of bias instrument for randomized trials. Our outcomes of interest include the rate of surgical site infection within 30 days of surgery, hospital length of stay, 30-day mortality, and treatment-related adverse effects. We will perform a contrast-based network meta-analysis using a frequentist random-effects model assuming a common heterogeneity parameter. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be utilized to assess the certainty of evidence for treatment effects., Discussion: By synthesizing evidence from available RCTs, this study will provide valuable insight for clinicians, patients, and health policymakers on the most effective antibiotics for preventing surgical site infection., Systematic Review Registration: PROSPERO CRD42023434544., (© 2024. The Author(s).)

Background: The diagnosis, etiology, and optimal management of fibromyalgia remains contentious. This uncertainty may result in variability in clinical management. We conducted a systematic review and meta-analysis of cross-sectional studies examining physicians' knowledge, attitudes, and practices regarding fibromyalgia., Methods: We searched MEDLINE, Embase, and PubMed from inception to February 2023 for cross-sectional surveys evaluating physicians' attitudes toward, and management of, fibromyalgia. Pairs of independent reviewers conducted article screening, data extraction, and risk of bias assessment in duplicate. We used random-effects meta-analysis to pool proportions for items reported by more than one study and the Grading of Recommendations Assessment, Development, and Evaluation approach to summarize the certainty of evidence., Results: Of 864 citations, 21 studies (8904 participants) were eligible for review. Most physicians endorsed fibromyalgia as a distinct clinical entity (84%; 95% confidence interval [CI], 74-92), and half (51%; 95% CI, 40-62) considered fibromyalgia a psychosocial condition. Knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%, 95% CI, 45-89) versus general practitioners (38%, 95% CI, 24-54) (P = .04). Symptom relief was endorsed as the primary management goal by most physicians (73%, 95% CI, 52-90). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were most endorsed for management of fibromyalgia, but with wide variability between surveys. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement., Conclusion: There is moderate certainty evidence to suggest that physicians are divided regarding whether fibromyalgia is a biomedical or psychosocial disorder. Physicians typically prioritize symptom relief as the primary goal of management, and often endorse management with exercise, non-opioid analgesics, nonsteroidal anti-inflammatory drugs, antidepressants, and physiotherapy (moderate to high certainty evidence); however, important practice variation exists., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Satisfactory management of postoperative pain remains challenging. Nonpharmacological modalities such as virtual and augmented reality (VR/AR) offer potential benefits and are becoming increasingly popular. This systematic review evaluates the effectiveness and safety of VR/AR interventions on postoperative pain and recovery., Methods: MEDLINE, Embase, CINAHL, Web of Science, and CENTRAL databases were searched from inception to July 27, 2023, for randomized controlled trials (RCTs), published in English, evaluating the use of VR/AR interventions for surgical pain relief. Study selection and data extraction were performed by pairs of reviewers independently and in duplicate, and potential risk of bias was determined using the Risk of Bias-version 2 (RoB 2) tool. Our outcomes included pain relief, reduction of anxiety, satisfaction, and adverse effects. Due to substantial heterogeneity, a narrative synthesis without meta-analysis was performed., Results: We included 35 trials among 2257 citations, categorized as surgery (n = 12), minor procedures (n = 15), and postoperative physiotherapy (n = 8). Surgical group included various surgeries, with 11 using immersive VR predominantly in the postoperative period, and most reporting no differences in pain, but potential for reduced anxiety and sedation requirements. In the minor procedures group, most studies reported decreased pain and anxiety during the procedural performance. Two studies reported increased heart rate, while 2 others reported better hemodynamic stability. Home-based AR physiotherapy achieved (n = 6) similar pain and functional outcomes after knee replacement, with 1 large study (n = 306) reporting reduction of mean costs by $2745 for provision of 12 weeks physiotherapy. There were some concerns around potential bias for most studies, as the nature of interventions make it challenging to blind assessors and participants. No important adverse effects were noted using VR/AR technology., Conclusions: Evidence from RCTs indicates that the use of immersive VR during minor procedures may reduce procedural pain, decrease anxiety, and improve satisfaction. However, small studies, inconsistent effect, and variation in the application of interventions are important limitations. Evidence to support the application of AR/VR for major surgeries is limited and needs to be further investigated. Use of home-based physiotherapy with AR likely has economic advantages, and facilitates virtual care for appropriate patients who can access and use the technology safely., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Background: Chronic postsurgical pain (CPSP) is common following musculoskeletal and orthopedic surgeries and is associated with impairment and reduced quality of life. Several interventions have been proposed to reduce CPSP; however, there remains uncertainty regarding which, if any, are most effective. We will perform a systematic review and network meta-analysis of randomised trials to assess the comparative benefits and harms of perioperative pharmacological and psychological interventions directed at preventing chronic pain after musculoskeletal and orthopedic surgeries., Methods: We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to present, without language restrictions. We will include randomised controlled trials that as follows: (1) enrolled adult patients undergoing musculoskeletal or orthopedic surgeries; (2) randomized them to any pharmacological or psychological interventions, or their combination directed at reducing CPSP, placebo, or usual care; and (3) assessed pain at 3 months or more after surgery. Screening for eligible trials, data extraction, and risk-of-bias assessment using revised Cochrane risk-of-bias tool (RoB 2.0) will be performed in duplicate and independently. Our main outcome of interest will be the proportion of surgical patients reporting any pain at ≥ 3 months after surgery. We will also collect data on other patient important outcomes, including pain severity, physical functioning, emotional functioning, dropout rate due to treatment-related adverse event, and overall dropout rate. We will perform a frequentist random-effects network meta-analysis to determine the relative treatment effects. When possible, the modifying effect of sex, surgery type and duration, anesthesia type, and veteran status on the effectiveness of interventions will be investigated using network meta-regression. We will use the GRADE approach to assess the certainty evidence and categorize interventions from most to least beneficial using GRADE minimally contextualised approach., Discussion: This network meta-analysis will assess the comparative effectiveness of pharmacological and psychological interventions directed at preventing CPSP after orthopedic surgery. Our findings will inform clinical decision-making and identify promising interventions for future research., Systematic Review Registration: PROSPERO CRD42023432503., (© 2024. The Author(s).)

Objective: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery., Data Sources: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice., Study Eligibility Criteria: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L., Methods: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty., Results: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures., Conclusion: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries., Data Sources: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis., Study Eligibility Criteria: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L., Methods: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty., Results: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures., Conclusion: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cognitive behavioural therapy (CBT) has been shown to be effective for several psychiatric and somatic conditions; however, most randomized controlled trials (RCTs) have administered treatment in person and whether remote delivery is similarly effective remains uncertain. We sought to compare the effectiveness of therapist-guided remote CBT and in-person CBT., Methods: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to July 4, 2023, for RCTs that enrolled adults (aged ≥ 18 yr) presenting with any clinical condition and that randomized participants to either therapist-guided remote CBT (e.g., teleconference, videoconference) or in-person CBT. Paired reviewers assessed risk of bias and extracted data independently and in duplicate. We performed random-effects model meta-analyses to pool patient-important primary outcomes across eligible RCTs as standardized mean differences (SMDs). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to assess the certainty of evidence and used the Instrument to Assess the Credibility of Effect Modification Analyses (ICEMAN) to rate the credibility of subgroup effects., Results: We included 54 RCTs that enrolled a total of 5463 patients. Seventeen studies focused on treatment of anxiety and related disorders, 14 on depressive symptoms, 7 on insomnia, 6 on chronic pain or fatigue syndromes, 5 on body image or eating disorders, 3 on tinnitus, 1 on alcohol use disorder, and 1 on mood and anxiety disorders. Moderate-certainty evidence showed little to no difference in the effectiveness of therapist-guided remote and in-person CBT on primary outcomes (SMD -0.02, 95% confidence interval -0.12 to 0.07)., Interpretation: Moderate-certainty evidence showed little to no difference in the effectiveness of in-person and therapist-guided remote CBT across a range of mental health and somatic disorders, suggesting potential for the use of therapist-guided remote CBT to facilitate greater access to evidence-based care. Systematic review registration: Open Science Framework (https://osf.io/7asrc)., Competing Interests: Competing interests:: Behnam Sadeghirad reports funding from the Canadian Institutes of Health Research, the Michael G. DeGroote Institute for Pain Research and Care, and the Chronic Pain Centre of Excellence for Canadian Veterans. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Introduction: A third of Canadian Armed Forces veterans report difficulty adjusting to post-military life. Moreover, an estimated 40% of Canadian veterans live with chronic pain, which is likely associated with greater needs during the transition from military to civilian life. This review explores challenges and transition needs among military personnel living with chronic pain as they return to civilian life., Methods: We searched MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to July 2022, for qualitative, observational, and mixed-method studies exploring transition needs among military veterans released with chronic pain. Reviewers, working independently and in duplicate, conducted screening and used a standardized and pilot-tested data collection form to extract data from all included studies. Content analysis was used to create a coding template to identify patterns in challenges and unmet needs of veterans transitioning to civilian life, and we summarized our findings in a descriptive manner., Results: Of 10,532 unique citations, we identified 43 studies that reported transition challenges and needs of military personnel; however, none were specific to individuals released with chronic pain. Most studies (41 of 43; 95%) focused on military personnel in general, with one study enrolling individuals with traumatic brain injury and another including homeless veterans. We identified military-to-civilian challenges in seven areas: (1) identity, (2) interpersonal interactions/relationships, (3) employment, (4) education, (5) finances, (6) self-care and mental health, and (7) accessing services and care., Conclusions: Military personnel who transition to civilian life report several important challenges; however, the generalizability to individuals released with chronic pain is uncertain. Further research is needed to better understand the transition experiences of veterans with chronic pain to best address their needs and enhance their well-being., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery., Background: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain., Methods: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty., Results: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer., Conclusions: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding., Competing Interests: P.J.K. received a research grant from the Focused Ultrasound Foundation (all unrelated to this manuscript). P.J.D. received research grants from Abbott Laboratories, CloudDX, Philips Healthcare, Roche Diagnostics, and Siemens (all unrelated to this manuscript). R.C., P.D.V., and K.A.O.T. are panel members of the European Society of Anesthesiology and Intensive Care (ESAIC) Task Force for the European Guidelines on Venous Thromboembolism (VTE). The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain., Design: Systematic review and network meta-analysis., Data Sources: EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021., Study Selection: Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks., Data Extraction and Synthesis: Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings., Results: Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) -1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI -0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI -4.72 to 5.59)., Conclusions: Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain., Prospero Registration Number: CRD42020185184., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)., Design: Systematic review and network meta-analysis of randomised clinical trials (RCTs)., Data Sources: MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023., Study Selection: Interventional RCTs that enrolled patients presenting with chronic pain associated with TMD., Data Extraction and Synthesis: Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We captured all reported patient-important outcomes, including pain relief, physical functioning, emotional functioning, role functioning, social functioning, sleep quality, and adverse events. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence and categorise interventions from most to least beneficial., Results: 233 trials proved eligible for review, of which 153-enrolling 8713 participants and exploring 59 interventions or combinations of interventions-were included in network meta-analyses. All subsequent effects refer to comparisons with placebo or sham procedures. Effects on pain for eight interventions were supported by high to moderate certainty evidence. The three therapies probably most effective for pain relief were cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (risk difference (RD) for achieving the minimally important difference (MID) in pain relief of 1 cm on a 10 cm visual analogue scale: 36% (95% CI 33 to 39)), therapist-assisted jaw mobilisation (RD 36% (95% CI 31 to 40)), and manual trigger point therapy (RD 32% (29 to 34)). Five interventions were less effective, yet more effective than placebo, showing RDs ranging between 23% and 30%: CBT, supervised postural exercise, supervised jaw exercise and stretching, supervised jaw exercise and stretching with manual trigger point therapy, and usual care (such as home exercises, self stretching, reassurance).Moderate certainty evidence showed four interventions probably improved physical functioning: supervised jaw exercise and stretching (RD for achieving the MID of 5 points on the short form-36 physical component summary score: 43% (95% CI 33 to 51)), manipulation (RD 43% (25 to 56)), acupuncture (RD 42% (33 to 50)), and supervised jaw exercise and mobilisation (RD 36% (19 to 51)). The evidence for pain relief or physical functioning among other interventions, and all evidence for adverse events, was low or very low certainty., Conclusion: When restricted to moderate or high certainty evidence, interventions that promote coping and encourage movement and activity were found to be most effective for reducing chronic TMD pain., Registration: PROSPERO (CRD42021258567)., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare: no financial support from any industry for the submitted work; no other relationships or activities that could appear to have influenced the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Chronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs., Methods: Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence., Results: Forty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45-62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005)., Conclusion: We found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids., Methods: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose., Interpretation: We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/)., Competing Interests: Competing interests: Corey Hayes reports support from the National Institute on Drug Abuse Clinical Trials Network (5UG1DA013732-23S3). David Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing. David Juurlink is also a member of the American College of Medical Toxicology. David Juurlink has received payment for lectures from Texas Tech University Health Sciences Centre and payment for expert testimony regarding analgesics, including opioids. He has received travel support for presentations and scientific meetings from the Canadian Institutes of Health Research, Stanford University and Texas Tech University Health Sciences Centre. Jason Busse is the Principal Investigator for the update of the 2017 Canadian Opioid Guideline, which is funded by Health Canada. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background/importance: Patient selection for spinal cord stimulation (SCS) therapy is crucial and is traditionally performed with clinical selection followed by a screening trial. The factors influencing patient selection and the importance of trialing have not been systematically evaluated., Objective: We report a narrative review conducted to synthesize evidence regarding patient selection and the role of SCS trials., Evidence Review: Medline, EMBASE and Cochrane databases were searched for reports (any design) of SCS in adult patients, from their inception until March 30, 2022. Study selection and data extraction were carried out using DistillerSR. Data were organized into tables and narrative summaries, categorized by study design. Importance of patient variables and trialing was considered by looking at their influence on the long-term therapy success., Findings: Among 7321 citations, 201 reports consisting of 60 systematic reviews, 36 randomized controlled trials (RCTs), 41 observational studies (OSs), 51 registry-based reports, and 13 case reports on complications during trialing were included. Based on RCTs and OSs, the median trial success rate was 72% and 82%, and therapy success was 65% and 61% at 12 months, respectively. Although several psychological and non-psychological determinants have been investigated, studies do not report a consistent approach to patient selection. Among psychological factors, untreated depression was associated with poor long-term outcomes, but the effect of others was inconsistent. Most RCTs except for chronic angina involved trialing and only one RCT compared patient selection with or without trial. The median (range) trial duration was 10 (0-30) and 7 (0-56) days among RCTs and OSs, respectively., Conclusions: Due to lack of a consistent approach to identify responders for SCS therapy, trialing complements patient selection to exclude patients who do not find the therapy helpful and/or intolerant of the SCS system. However, more rigorous and large studies are necessary to better evaluate its role., Competing Interests: Competing interests: SN and DAP are editors for RAPM. All other authors declare no conflicts of interest., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Accurate measurement of health status is essential to assess veterans' needs and the effects of interventions directed at improving veterans' well-being. We conducted a systematic review to identify instruments that measure subjective health status, considering four components (ie, physical, mental, social or spiritual well-being)., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, JSTOR, ERIC, Social Sciences Abstracts and ProQuest in June 2021 for studies reporting on the development or evaluation of instruments measuring subjective health among outpatient populations. We assessed risk of bias with the Consensus-based Standards for the Selection of Health Measurement Instruments tool and engaged three veteran partners to independently assess the clarity and applicability of identified instruments., Results: Of 5863 abstracts screened, we identified 45 eligible articles that reported health-related instruments in the following categories: general health (n=19), mental health (n=7), physical health (n=8), social health (n=3) and spiritual health (n=8). We found evidence for adequate internal consistency for 39 instruments (87%) and good test-retest reliability for 24 (53%) instruments. Of these, our veteran partners identified five instruments for the measurement of subjective health (Military to Civilian Questionnaire (M2C-Q), Veterans RAND 36-Item Health Survey (VR-36), Short Form 36, Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Sleep Health Scale) as clear and very applicable to veterans. Of the two instruments developed and validated among veterans, the 16-item M2C-Q considered most components of health (mental, social and spiritual). Of the three instruments not validated among veterans, only the 26-item WHOQOL-BREF considered all four components of health., Conclusion: We identified 45 health measurement instruments of which, among those reporting adequate psychometric properties and endorsed by our veteran partners, 2 instruments showed the most promise for measurement of subjective health. The M2C-Q, which requires augmentation to capture physical health (eg, the physical component score of the VR-36), and the WHOQOL-BREF, which requires validation among veterans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management., Methods: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study., Results: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score., Conclusions: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The purpose of this review was to examine the reporting in chiropractic mixed methods research using Good Reporting of A Mixed Methods Study (GRAMMS) criteria., Methods: In this methodological review, we searched MEDLINE, Embase, CINAHL, and the Index to Chiropractic Literature from the inception of each database to December 31, 2020, for chiropractic studies reporting the use of both qualitative and quantitative methods or mixed qualitative methods. Pairs of reviewers independently screened titles, abstracts, and full-text studies, extracted data, and appraised reporting using the GRAMMS criteria and risk of bias with the Mixed Methods Appraisal Tool (MMAT). Generalized estimating equations were used to explore factors associated with reporting using GRAMMS criteria., Results: Of 1040 citations, 55 studies were eligible for review. Thirty-seven of these 55 articles employed either a multistage or convergent mixed methods design, and, on average, 3 of 6 GRAMMS items were reported among included studies. We found a strong positive correlation in scores between the GRAMMS and MMAT instruments (r = 0.78; 95% CI, 0.66-0.87). In our adjusted analysis, publications in journals indexed in Web of Science (adjusted odds ratio = 2.71; 95% CI, 1.48-4.95) were associated with higher reporting using GRAMMS criteria. Three of the 55 studies fully adhered to all 6 GRAMMS criteria, 4 studies adhered to 5 criteria, 10 studies adhered to 4 criteria, and the remaining 38 adhered to 3 criteria or fewer., Conclusion: Our findings suggest that reporting in chiropractic mixed methods research using GRAMMS criteria was poor, particularly among studies with a higher risk of bias., (Copyright © 2023. Published by Elsevier Inc.)

Background: Among patients who had an ischaemic stroke presenting directly to a stroke centre where endovascular thrombectomy (EVT) is immediately available, there is uncertainty regarding the role of intravenous thrombolysis agents before or concurrently with EVT. To support a rapid guideline, we conducted a systematic review and meta-analysis to examine the impact of EVT alone versus EVT with intravenous alteplase in patients who had an acute ischaemic stroke due to large vessel occlusion., Methods: In November 2021, we searched MEDLINE, Embase, PubMed, Cochrane, Web of Science, clincialtrials.gov and the ISRCTN registry for randomised controlled trials (RCTs) comparing EVT alone versus EVT with alteplase for acute ischaemic stroke. We conducted meta-analyses using fixed effects models and assessed the certainty of evidence using the GRADE approach., Results: In total 6 RCTs including 2334 participants were eligible. Low certainty evidence suggests that, compared with EVT and alteplase, there is possibly a small decrease in the proportion of patients independent with EVT alone (risk ratio (RR) 0.97, 95% CI 0.89 to 1.05; risk difference (RD) -1.5%; 95% CI -5.4% to 2.5%), and possibly a small increase in mortality with EVT alone (RR 1.07, 95% CI 0.88 to 1.29; RD 1.2%, 95% CI -2.0% to 4.9%) . Moderate certainty evidence suggests that there is probably a small decrease in symptomatic intracranial haemorrhage (sICH) with EVT alone (RR 0.75, 95% CI 0.52 to 1.07; RD -1.0%; 95%CI -1.8% to 0.27%)., Conclusions: Low certainty evidence suggests that there is possibly a small decrease in the proportion of patients that achieve functional independence and a small increase in mortality with EVT alone. Moderate certainty evidence suggests that there is probably a small decrease in sICH with EVT alone. The accompanying guideline provides contextualised guidance based on this body of evidence., Prospero Registration Number: CRD42021249873., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomatic PHPT, who are not candidates for parathyroid surgery, cinacalcet probably reduced serum calcium and PTH levels; anti-resorptives increased bone density. For patients with asymptomatic PHPT, surgery usually achieves biochemical cure. These results can help to inform patients and clinicians regarding use of medical therapy and surgery in PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials., Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials to March 2021 for studies that enrolled patients with chronic non-cancer pain, randomised them to receive different opioids, or opioids vs placebo, and followed them for at least 4 weeks. Certainty of evidence was evaluated using the GRADE approach., Results: We identified 82 eligible trials (22 619 participants) that evaluated 14 opioids. Compared with placebo, several opioids showed superiority to others for analgesia and improvement in physical function; however, when restricted to pooled-effect estimates supported by moderate certainty evidence, no differences between opioids were evident. Among opioids with moderate certainty evidence, all increased the risk of gastrointestinal adverse events compared with placebo, although no opioids were more harmful than others. Low to very low certainty evidence suggests that extended-release vs immediate-release opioids may provide similar benefits for pain relief and physical functioning, and gastrointestinal harms., Conclusions: Our findings support the pooling of effect estimates across different types and formulations of opioids to inform effectiveness for chronic non-cancer pain., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Several specialized collections of COVID-19 literature have been developed during the global health emergency. These include the WHO COVID-19 Global Literature Database, Cochrane COVID-19 Study Register, CAMARADES COVID-19 SOLES, Epistemonikos' COVID-19 L-OVE, and LitCovid. Our objective was to evaluate the completeness of these collections and to measure the time from when COVID-19 articles are posted to when they appear in the collections., Study Design and Setting: We tested each selected collection for the presence of 440 included studies from 25 COVID-19 systematic reviews. We sampled 112 journals and prospectively monitored their websites until a new COVID-19 article appeared. We then monitored for 2 weeks to see when the new articles appeared in each collection. PubMed served as a comparator., Results: Every collection provided at least one record not found in PubMed. Four records (1%) were not in any of the sources studied. Collections contained between 83% and 93% of the primary studies with the WHO database being the most complete. By 2 weeks, between 60% and 78% of tracked articles had appeared., Conclusion: Our findings support the use of the best performing COVID-19 collections by systematic reviews to replace paywalled databases., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain., Objective: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD., Methods: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses., Results: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty., Conclusion: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials., Trial Registration: PROSPERO Identifier: CRD42021238486., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the risk of bias in chiropractic mixed methods research., Methods: We performed a secondary analysis of a meta-epidemiological review of chiropractic mixed methods studies. We assessed risk of bias with the Mixed Methods Appraisal Tool (MMAT) and used generalized estimating equations to explore factors associated with risk of bias., Results: Among 55 eligible studies, a mean of 62% (6.8 [2.3]/11) of MMAT items were fulfilled. In our adjusted analysis, studies published since 2010 versus pre-2010 (adjusted odds ratio [aOR] = 2.26; 95% confidence interval [CI], 1.39 to 3.68) and those published in journals with an impact factor versus no impact factor (aOR = 2.21; 95% CI, 1.33 to 3.68) were associated with lower risk of bias., Conclusion: Our findings suggest opportunities for improvement in the quality of conduct among published chiropractic mixed methods studies. Author compliance with the MMAT criteria may reduce methodological bias in future mixed methods research., Competing Interests: The authors have no disclaimers, competing interests, or sources of support or funding to report in the preparation of this manuscript. Dr. Emary is supported by research grants from McMaster University, the NCMIC Foundation, and the Canadian Chiropractic Research Foundation outside of the submitted work. Dr. Busse is funded, in part, by a Canada Research Chair in the prevention and management of chronic pain from the Canadian Institutes of Health Research Fellowship Award., (© JCCA 2022.)

Study Objectives: We conducted a systematic review to explore the effectiveness of medical cannabis for impaired sleep., Methods: We searched MEDLINE, EMBASE, CENTRAL, and PsychINFO to January 2021 for randomized trials of medical cannabis or cannabinoids for impaired sleep vs. any non-cannabis control. When possible, we pooled effect estimates for all patient-important sleep-related outcomes and used the GRADE approach to appraise the certainty of evidence., Results: Thirty-nine trials (5100 patients) were eligible for review, of which 38 evaluated oral cannabinoids and 1 administered inhaled cannabis. The median follow-up was 35 days, and most trials (33 of 39) enrolled patients living with chronic cancer or noncancer chronic pain. Among patients with chronic pain, moderate certainty evidence found that medical cannabis probably results in a small improvement in sleep quality versus placebo (modeled risk difference [RD] for achieving the minimally important difference [MID], 8% [95% CI, 3 to 12]). Moderate to high certainty evidence shows that medical cannabis vs. placebo results in a small improvement in sleep disturbance for chronic non-cancer pain (modeled RD for achieving the MID, 19% [95% CI, 11 to 28]) and a very small improvement in sleep disturbance for chronic cancer pain (weighted mean difference of -0.19 cm [95%CI, -0.36 to -0.03 cm]; interaction p = .03). Moderate to high certainty evidence shows medical cannabis, versus placebo, results in a substantial increase in the risk of dizziness (RD 29% [95%CI, 16 to 50], for trials with ≥3 months follow-up), and a small increase in the risk of somnolence, dry mouth, fatigue, and nausea (RDs ranged from 6% to 10%)., Conclusion: Medical cannabis and cannabinoids may improve impaired sleep among people living with chronic pain, but the magnitude of benefit is likely small., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We conducted a systematic review and meta-analysis to assess effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as adjuncts for postoperative pain management., Methods: We searched seven databases and two trial registers from inception to February 2021 for RCTs that compared SSRIs or SNRIs with placebo or an active control for postoperative pain management., Results: We included 24 RCTs with 2197 surgical patients (21 trials for SNRIs and three trials for SSRIs). Moderate-quality evidence found that, compared with placebo, SSRIs/SNRIs (majority SNRIs) significantly reduced postoperative pain within 6 h {weighted mean difference (WMD) -0.73 cm on a 10 cm VAS (95% confidence interval [CI]: -1.04 to -0.42)}, 12 h (-0.68 cm [-1.28 to -0.07]), 24 h (-0.68 cm [-1.16 to -0.20]), 48 h (-0.73 cm [-1.22 to -0.23]), 10 days to 1 month (-0.71 cm [-1.11 to -0.31]), 3 months (-0.64 cm [-1.05 to -0.22]), and 6 months (-0.95 cm [-1.64 to -0.25]), and opioid consumption within 24 h (WMD -12 mg [95% CI: -16 to -8]) and 48 h (-10 mg [-15 to -5]), and improved patient satisfaction (WMD 0.49 point on a 1-4 Likert scale [95% CI: 0.09 to 0.89]) without significant increase in adverse events. Selective serotonin reuptake inhibitors tended to be less effective despite non-significant subgroup effects., Conclusions: Serotonin-norepinephrine reuptake inhibitors as an adjunct to standard perioperative care probably provide small reduction in both acute and chronic postoperative pain and opioid consumption, and small improvement in patient satisfaction without increases in adverse events. The effects of SSRIs are inconclusive because of very limited evidence., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries., Methods: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty., Discussion: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach., Systematic Review Registration: PROSPERO CRD42021234119., (© 2021. The Author(s).)

Background: Mixed methods designs are increasingly used in health care research to enrich findings. However, little is known about the frequency of use of this methodology in chiropractic research, or the quality of reporting among chiropractic studies using mixed methods., Objective: To quantify the use and quality of mixed methods in chiropractic research, and explore the association of study characteristics (e.g., authorship, expertise, journal impact factor, country and year of publication) with reporting quality., Methods: We will conduct a systematic search of MEDLINE, EMBASE, CINAHL, and the Index to Chiropractic Literature to identify all chiropractic mixed methods studies published from inception of each database to December 31, 2020. Articles reporting the use of both qualitative and quantitative methods, or mixed qualitative methods, will be included. Pairs of reviewers will perform article screening, data extraction, risk of bias with the Mixed Methods Appraisal Tool (MMAT), and appraisal of reporting quality using the Good Reporting of A Mixed Methods Study (GRAMMS) guideline. We will explore the correlation between GRAMMS and MMAT scores, and construct generalized estimating equations to explore factors associated with reporting quality., Discussion: This will be the first methodological review to examine the reporting quality of published mixed methods studies involving chiropractic research. The results of our review will inform opportunities to improve reporting in chiropractic mixed methods studies. Our results will be disseminated in a peer-reviewed publication and presented publicly at conferences and as part of a doctoral thesis., (© 2021. The Author(s).)

Objective: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain., Design: Systematic review and meta-analysis., Data Sources: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021., Study Selection: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up., Data Extraction and Synthesis: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence., Results: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect)., Conclusions: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form www.icmje.org/disclosure-of-interest/ and declare: no financial support from any industry for the submitted work; IP and SU have received research funds from Northern Green Canada; IP has been a paid consultant for Northern Green Science, Northern Green Canada, Monk-E psychedelics, and Evergreen Pacific Insurance Corporation; SU and IP received honoraria from Spectrum Therapeutics and Tilray Inc. for educational presentations; MAW is the chief medical officer for Canopy Growth Corporation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain., Design: Systematic review., Data Sources: CENTRAL, EMBASE and MEDLINE., Main Outcomes and Measures: Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events., Study Selection Criteria and Methods: We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome., Results: Eligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) -3.4 milligram morphine equivalent (MME); 95% CI (CI) -12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD -0.18 cm; 95% CI -0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD -0.22 cm; 95% CI -0.4 to -0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD -1%; 95% CI -4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD -22.5 MME; 95% CI -43.06 to -1.97)., Conclusion: Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence. PROSPERO registration number CRD42018091098., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chronic, non-cancer, axial or radicular spinal pain is a common condition associated with considerable socioeconomic burden. Clinicians frequently offer patients various interventional procedures for the treatment of chronic spine pain; however, the comparative effectiveness and safety of available procedures remains uncertain., Methods: We will conduct a systematic review of randomised controlled trials that explores the effectiveness and harms of interventional procedures for the management of axial or radicular, chronic, non-cancer, spine pain. We will identify eligible studies through a systematic search of Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Web of Science from inception without language restrictions. Eligible trials will: (1) enrol primarily adult patients (≥18 years old) with axial or radicular, chronic, non-cancer, spine pain, (2) randomise patients to different, currently available, interventional procedures or to an interventional procedure and a placebo/sham procedure or usual care, and (3) measure outcomes at least 1 month after randomisation.Pairs of reviewers will independently screen articles identified through searches and extract information and assess risk of bias of eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. We will use frequentist random-effects network meta-analyses to assess the relative effects of interventional procedures, and five a priori hypotheses to explore between studies subgroup effects. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome, including direct, indirect and network estimates., Ethics and Dissemination: No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence., Prospero Registration Number: CRD42020170667., Competing Interests: Competing interests: DNB and CJS declare intellectual and financial conflicts of interest, as pain physicians that perform interventional procedures for chronic spinal complaints as part of their practices. BS and TA are member of the GRADE Working Group., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To compare different modalities of renal replacement therapy in critically ill adults with acute kidney injury., Data Sources: We searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 25 May, 2020. We included randomized controlled trials comparing the efficacy and safety of different renal replacement therapy modalities in critically ill patients with acute kidney injury., Study Selection: Ten reviewers (working in pairs) independently screened studies for eligibility, extracted data, and assessed risk of bias., Data Extraction: We performed random-effects frequentist network meta-analyses and used the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess certainty of evidence. The primary analysis was a four-node analysis: continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and peritoneal dialysis. The secondary analysis subdivided these four nodes into nine nodes including continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, continuous veno-venous hemodiafiltration, continuous arterio-venous hemodiafiltration, intermittent hemodialysis, intermittent hemodialysis with hemofiltration, slow efficiency extended dialysis, slow efficiency extended dialysis with hemofiltration, and peritoneal dialysis. We set the minimal important difference threshold for mortality as 2.5% (relative difference, 0.04)., Data Synthesis: Thirty randomized controlled trials ( n = 3,774 patients) proved eligible. There may be no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis (relative risk, 1.04; 95% CI, 0.93-1.18; low certainty), whereas continuous renal replacement therapy demonstrated a possible increase in mortality compared with slow efficiency extended dialysis (relative risk, 1.06; 95% CI, 0.85-1.33; low certainty) and peritoneal dialysis (relative risk, 1.16; 95% CI, 0.92-1.49; low certainty). Continuous renal replacement therapy may increase renal recovery compared with intermittent hemodialysis (relative risk, 1.15; 95% CI, 0.91-1.45; low certainty), whereas both continuous renal replacement therapy and intermittent hemodialysis may be worse for renal recovery compared with slow efficiency extended dialysis and peritoneal dialysis (low certainty). Peritoneal dialysis was probably associated with the shortest duration of renal support and length of ICU stay compared with other interventions (low certainty for most comparisons). Slow efficiency extended dialysis may be associated with shortest length of hospital stay (low or moderate certainty for all comparisons) and days of mechanical ventilation (low certainty for all comparisons) compared with other interventions. There was no difference between continuous renal replacement therapy and intermittent hemodialysis in terms of hypotension (relative risk, 0.92; 95% CI, 0.72-1.16; moderate certainty) or other complications of therapy, but an increased risk of hypotension and bleeding was seen with both modalities compared with peritoneal dialysis (low or moderate certainty). Complications of slow efficiency extended dialysis were not sufficiently reported to inform comparisons., Conclusions: The results of this network meta-analysis suggest there is no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis although continuous renal replacement therapy may increases renal recovery compared with intermittent hemodialysis. Slow efficiency extended dialysis with hemofiltration may be the most effective intervention at reducing mortality. Peritoneal dialysis is associated with good efficacy, and the least number of complications however may not be practical in all settings. Importantly, all conclusions are based on very low to moderate certainty evidence, limited by imprecision. At the very least, ICU clinicians should feel comfortable that the differences between continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and, where clinically appropriate, peritoneal dialysis are likely small, and any of these modalities is a reasonable option to employ in critically ill patients., Competing Interests: Dr. Collister reports personal fees from Akebia, outside the submitted work. Dr. Bagshaw reported grants and personal fees from Baxter, during the conduct of the study; personal fees from CNA Diagnostics, personal fees from BioPorto, outside the submitted work. Dr. Wald received grants and personal fees from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Competing Interests: Intérêts concurrents: Bram Rochwerg est un chercheur participant à un essai financé par une subvention des Instituts de recherche en santé du Canada qui évalue les effets des corticostéroïdes chez les patients atteints de la COVID-19. Aucun autre intérêt concurrent déclaré.

Competing Interests: Intérêts concurrents: Ning Shen effectue de la recherche dans le cadre d’un essai clinique financé par le Centre des sciences de la santé de l’Université de Pékin portant sur les effets de l’hydroxychloroquine chez les patients atteints de la COVID-19. Aucun autre intérêt concurrent n’a été déclaré.

Background: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue., Methods: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence., Results: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%)., Conclusions: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses., Methods: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects., Results: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia., Interpretation: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality., Competing Interests: Competing interests: Bram Rochwerg is an investigator in a trial, supported by a Canadian Institute of Health Research grant, evaluating the effect of corticosteroids in COVID-19 patients. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19., Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes., Results: In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting., Interpretation: To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence., Competing Interests: Competing interests: Ning Shen is an investigator in a clinical trial evaluating the effect of hydroxychloroquine in patients with coronavirus disease 2019 that is funded by the Peking University Health Science Center. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Objective: The association of American Medical Association's (AMA) Guides edition with impairment ratings is uncertain., Methods: We used data from a consecutive sample of 249 injured workers referred for an independent evaluation 10 months before and after assessors switched from the 5th to the 6th edition of the AMA Guides., Results: The median whole person impairment rating was 7.0% (interquartile range [IQR]: 4 to 14) for 131 claimants assessed with the 5th edition of the Guides, and 4.0% (IQR: 2 to 8) for 118 claimants assessed with the 6th edition (P-value for difference: 0.002). Multivariable analysis showed a 36.4% relative reduction (95% confidence interval [CI] 17.2% to 57.3%) in impairment rating with the 6th edition of the Guides versus the 5th edition., Conclusions: The 6th edition of the AMA Guides provides systematically lower impairment ratings for injured workers than the 5th edition.

Purpose Breast cancer surgery is associated with unemployment. Identifying high-risk patients could help inform strategies to promote return to work. We systematically reviewed observational studies to explore factors associated with unemployment after breast cancer surgery. Methods We searched MEDLINE, EMBASE, CINAHL, and PsycINFO to identify studies that explored risk factors for unemployment after breast cancer surgery. When possible, we pooled estimates of association for all independent variables reported by more than one study. Results Twenty-six studies (46,927 patients) reported the association of 127 variables with unemployment after breast cancer surgery. Access to universal health care was associated with higher rates of unemployment (26.6% v 15.4%; test of interaction P = .05). High-quality evidence showed that unemployment after breast cancer surgery was associated with high psychological job demands (odds ratio [OR], 4.26; 95% CI, 2.27 to 7.97), childlessness (OR, 1.30; 95% CI, 1.11 to 1.53), lower education level (OR, 1.15; 95% CI, 1.05 to 1.25), lower income level (OR, 1.46; 95% CI, 1.24 to 1.73), cancer stage II, III or IV (OR, 1.43; 95% CI, 1.13 to 1.82), and mastectomy versus breast-conserving surgery (OR, 1.18; 95% CI, 1.07 to 1.30). Moderate-quality evidence suggested an association with high physical job demands (OR, 2.11; 95%CI, 1.52 to 2.93), African-American ethnicity (OR, 1.89; 95% CI, 1.21 to 2.96), and receipt of chemotherapy (OR, 1.95; 95% CI, 1.36 to 2.79). High-quality evidence demonstrated no significant association with part-time hours, blue-collar work, tumor size, positive lymph nodes, or receipt of radiotherapy or endocrine therapy; moderate-quality evidence suggested no association with age, marital status, or axillary lymph node dissection. Conclusion Addressing high physical and psychological job demands may be important in reducing unemployment after breast cancer surgery.

Background: Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising., Methods: We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence., Results: Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]., Conclusions: Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome., Clinical Trial Registration: PROSPERO CRD42016047335., (Copyright © 2017. Published by Elsevier Ltd.)

Competing Interests: Competing interests: D. Norm Buckley and Jason Busse report grants from Health Canada during the conduct of the study. Jason Busse received grants from the Canadian Institutes of Health Research (CIHR) during the conduct of the study. D. Norm Buckley reports grants from Purdue Pharma and Janssen Inc. outside the submitted work. Chris Cull received personal fees from Indivior. David Juurlink reports grants from CIHR and from the Ontario Ministry of Health and Long-Term Care, and personal fees outside the submitted work. Sol Stern was a member of advisory boards for Astra Zeneca, Bristol-Myers Squibb and Johnson and Johnson; received fees for expert opinions from the Canadian Medical Protective Association; received consulting fees from mdBriefCase.com, Ethypharm and Sea Courses; and received honoraria for Continuing Medical Education presentations from Purdue Pharma and Paladin. No other competing interests were declared.

Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer., Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase., Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy., Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery., (© 2016 Canadian Medical Association or its licensors.)